Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial
| العنوان: | Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial |
|---|---|
| المؤلفون: | Onyema Ogbuagu, Peter J Ruane, Daniel Podzamczer, Laura C Salazar, Keith Henry, David M Asmuth, David Wohl, Richard Gilson, Yongwu Shao, Ramin Ebrahimi, Stephanie Cox, Alexander Kintu, Christoph Carter, Moupali Das, Jared M Baeten, Diana M Brainard, Gary Whitlock, Jason M Brunetta, Gitte Kronborg, Christoph D Spinner, Andrea Antinori, Vanessa Apea, David Asmuth, Ann Avery, Paul Benson, Colm Bergin, Mezgebe Berhe, Indira Brar, Cynthia Brinson, Jason Brunetta, Jeffrey Burack, Thomas Campbell, Michelle Cespedes, Amanda Clarke, Megan Coleman, Josep Coll, Manuel Crespo Casal, Catherine Creticos, Gordon Crofoot, Frederick Cruickshank, Eric Cua, Eric Daar, Joseph de Wet, Edwin DeJesus, Jorge Del Romero Guerrero, William Dinges, Susanne Doblecki-Lewis, Taylor Donovan, Olamide Dosekun, Jason Flamm, Joel Gallant, Jan Gerstoft, Jay Gladstein, Robert Grant, Robert Grossberg, Bernhard Haas, Jason Halperin, W. David Hardy, Charles Hare, Shawn Hassler, Richard Hengel, William Henry, Theo Hodge, Sybil Hosek, Christopher Hurt, Michelle Iandiorio, Heiko Jessen, Stephen Kegg, Gabriele Knecht, Ivanka Krznaric, Anthony LaMarca, Carsten Schade Larsen, Olav Ditlevsen Larsen, Adriano Lazzarin, Clifford Leen, Christopher Lucasti, Patrick Mallon, Sharon Mannheimer, Martin Markowitz, Claudia Martorell, Kenneth Mayer, Anthony Mills, Jean-Michel Molina, Sheldon Morris, Karam Mounzer, Nneka Nwokolo, Olayemi Osiyemi, Andrew Petroll, Patrick Philibert, John Phoenix, Gilles Pialoux, Frank Post, Maria Prins, Moti Ramgopal, Bruce Rashbaum, Iain Reeves, Gary Richmond, Armin Rieger, Peter Ruane, Laura Salazar, Anthony Scarsella, Gabriel Schembri, Mia Scott, Peter Shalit, Gary Sinclair, Magdalena Sobieszczyk, Christoph Spinner, Jeffrey Stephens, Jason Szabo, Stephen Taylor, Melanie Thompson, Cecile Tremblay, Benoit Trottier, Gene Voskuhl, Barbara Wade, Kimberly Workowski, Sigal Yawetz, Benjamin Young |
| المساهمون: | Infectious diseases, AII - Infectious diseases, APH - Global Health |
| المصدر: | The Lancet HIV, 8(7), e397-e407. Elsevier Limited DISCOVER study team 2021, ' Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis : week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial ', The Lancet HIV, vol. 8, no. 7, pp. e397-e407 . https://doi.org/10.1016/S2352-3018Test(21)00071-0 |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Anti-HIV Agents, Epidemiology, Immunology, Organophosphonates, HIV Infections, Emtricitabine, Placebo, Tenofovir alafenamide, law.invention, Young Adult, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacotherapy, Double-Blind Method, Randomized controlled trial, law, Virology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Tenofovir, Aged, Alanine, business.industry, Adenine, Incidence (epidemiology), virus diseases, Middle Aged, 030112 virology, Clinical trial, Treatment Outcome, Infectious Diseases, HIV-1, Drug Therapy, Combination, Female, Pre-Exposure Prophylaxis, business, Follow-Up Studies, medicine.drug |
| الوصف: | Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences. |
| وصف الملف: | application/pdf |
| تدمد: | 2352-3018 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::303b5922ad83d78a448781b8c096428cTest https://doi.org/10.1016/s2352-3018Test(21)00071-0 |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....303b5922ad83d78a448781b8c096428c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523018 |
|---|